A method, device and system for rapid screening and triage of in-situ / environmental ionization mass spectrometry of target residues in industrial samples

Abstract

This invention relates to the field of industrial quality control and rapid mass spectrometry analysis technology, and discloses a method, device, and system for rapid in-situ / environmental ionization mass spectrometry screening and split determination of target residues in industrial samples. This method addresses time-sensitive scenarios such as incoming material acceptance, process anomaly location, on-site inspection, and emergency splitting. It tackles the challenges of complex industrial sample matrices, low target analyte content, and the need for enrichment and long cycles for confirmatory detection. The method constructs a closed-loop process: "minimalist sampling / introduction – in-situ / environmental ionization – mass spectrometry acquisition – background reference – candidate ion set – matching and exclusion discrimination – splitting decision output." The method acquires sample and background reference spectra within the same acquisition time window or equivalent time window. Candidate feature ion sets are extracted through background subtraction / difference spectroscopy. Combined with repeatability stability, sample / background contrast thresholds, and isotope / adjunct / accompanying ion consistency rules, reference fingerprint database matching and environmental background / non-target spectral exclusion are performed. The system outputs a screening conclusion of "suspected presence / suspected absence / requires verification" and provides triage suggestions for further confirmation (GC-MS, LC-MS / MS, or tandem mass spectrometry). The system integrates sampling / introduction, ionization, mass spectrometry detection, and data processing decision modules. It is adaptable to gas / liquid / solid samples, covering volatile and transpolar molecular systems, and offers advantages such as high speed, low preparation cost, engineerable deployment, and reduced risk of misjudgment.

Description

Technical Field

[0001] This invention relates to the fields of industrial quality control, rapid screening of industrial samples and mass spectrometry analysis, and in particular to an analytical method, apparatus and system for rapidly screening target residues or characteristic components in industrial samples by in-situ / environmental ionization and mass spectrometry detection under normal or near-normal pressure conditions, and for outputting a diversion judgment based on the same-window background reference, fingerprint matching and exclusion rules. Background Technology

[0002] In industrial systems such as polyurethane, coatings, adhesives, plasticizers, polyether / polyester polyols, solvents, and polymeric additives, low-content target residues (e.g., aldehydes and ketones, process byproducts, low-molecular-weight additives, migratable substances, or unusual contaminants) can significantly affect odor, VOC / emission indicators, product consistency, and end-application performance. Common challenges in industrial settings include: complex sample matrices, high viscosity, or a high concentration of high-boiling-point components, making target signals susceptible to matrix effects; target content may be at the ppb or ppt level; and large sample volumes and early decision-making points in on-site and incoming material acceptance scenarios, making it difficult to promptly cover the first decision point relying solely on laboratory confirmation.

[0003] Existing methods often employ confirmatory techniques such as GC-MS, HS-GC-MS, and LC-MS / MS. While these methods offer both qualitative and quantitative analysis, they typically require enrichment, complex sample preparation, or lengthy chromatographic procedures, resulting in high time complexity and cost. When companies only need information such as "whether the target residue is suspected" and "in which sample / batch / time window is the residue more likely to be present" to guide decision-making regarding the confirmation process, the existing workflow is inefficient.

[0004] Direct mass spectrometry and environmental / in-situ ionization can acquire samples rapidly under low preparation conditions, but they still have problems in industrial sample scenarios, such as interference from environmental / system background ions, misinterpretation due to complex spectra, open ionization fluctuations, and lack of engineerable interpretation rules and split output mechanisms.

[0005] Therefore, there is an urgent need for a rapid screening and triage technology for industrial samples: a technology that is compatible with gas / liquid / solid samples, covers volatile and transpolar molecular systems, requires no or only minimal pretreatment, reduces the risk of misjudgment through peer background reference and fingerprint discrimination rules, and outputs a decision-making closed loop for "rapid screening-triage-confirmation". Summary of the Invention

[0006] (a) Purpose of the invention This invention provides a method, apparatus, and system for rapid in-situ / environmental ionization mass spectrometry screening and split determination of target residues in industrial samples, so as to achieve rapid screening, stable interpretation, and split output under low preparation conditions, and solve the problems of low content targets, complex matrices, and difficulty in moving the confirmation link forward in industrial samples.

[0007] (II) Technical Solution 1. Methodology and Scheme A rapid in-situ / environmental ionization mass spectrometry screening and split determination method for target residues in industrial samples includes the following steps: (1) Sample acquisition and sampling / introduction method selection: Acquire the industrial sample to be tested, and the sample form is at least one of gaseous, liquid or solid, covering volatile and transpolar molecular systems; select at least one sampling / introduction method according to the sample form and introduce the sample into the ionization region.

[0008] (2) Minimalist pretreatment (optional): Minimalist pretreatment is selected based on the sample matrix; the pretreatment does not include systematic separation and long-term purification, and does not exceed the acceptable complexity of the industrial site, including but not limited to settling, dilution, short-term shaking, simple filtration or closed container equilibration to form headspace.

[0009] (3) In-situ / environmental ionization and mass spectrometry acquisition: In-situ / environmental ionization is used under normal or near-normal pressure to form analytical ions in the sample, and the ions are introduced into the mass spectrometry detection unit for acquisition to obtain sample mass spectrometry data within at least one acquisition time window.

[0010] (4) Obtaining the background reference spectrum: Within the same acquisition time window as step (3) or within a window that meets the equivalence condition, obtain the background reference spectrum; the background reference spectrum includes at least one of the following: air background spectrum, system baseline spectrum, blank carrier spectrum, blank headspace spectrum or valve switching blank gas path spectrum.

[0011] (5) Extraction of candidate feature ion set: The sample spectrum and the background reference spectrum are subjected to background subtraction, difference spectrum calculation or relative intensity adjustment to obtain the difference spectrum; the candidate feature ion set is extracted from the difference spectrum and at least one robustness rule is applied, including: stable appearance after repeated injection; the sample spectrum is significantly higher than the background reference spectrum (exceeding the preset multiple threshold or statistical threshold); the isotope peak / addition ion / accompanying ion consistency relationship is satisfied; and the preset mass deviation window is satisfied.

[0012] (6) Matching and discrimination: Match the candidate feature ion set with the reference fingerprint library; the reference fingerprint library includes, but is not limited to, standard / control sample fingerprints, compliance baseline batch fingerprints, target ion list and its accompanying ion relationship rule set.

[0013] (7) Exclusion discrimination: Exclusion discrimination is performed on the fingerprints of environmental background / system background ions, non-target spectrums unrelated to the target, and control group ions with similar structures; exclusion can be achieved based on rules such as missing control characteristic ions, invalid control pairing relationship, and background ratio exceeding the threshold.

[0014] (8) Screening conclusion and triage decision output: Based on the combined results of matching and exclusion discrimination, output the screening conclusion and the triage suggestion of whether to enter the subsequent confirmation process; the subsequent confirmation process includes GC-MS, LC-MS / MS, tandem mass spectrometry fragmentation verification or quantitative methodologies with standard curve / internal standard strategy.

[0015] (9) Archiving and Traceability (optional): The sample spectrum and the background reference spectrum are associated and stored in pairs, and a report containing the paired spectrum, candidate ion set, screening conclusion and diversion suggestion is output for quality control archiving or traceability.

[0016] The above discrimination rules can be implemented through manual interpretation, semi-automatic processing, or automatic processing. This invention does not limit the specific implementation method.

[0017] The threshold, window, or discrimination condition can be set according to the specific application scenario, sample type, and instrument conditions. This invention does not limit the specific value of these conditions.

[0018] The reference fingerprint database can be pre-established, gradually constructed, or temporarily selected. This invention does not limit its storage form, scale, or construction method.

[0019] 2. System Solution A rapid screening and triage system for industrial sample target residues used to implement the above method includes: The sampling / introduction module is used to realize at least one sample introduction method such as dip / drop, carrier carrying, headspace / desorption, and near-field introduction, and may include a heatable desorption unit and a gas path / valve switching unit; The ionization module is used to form analytical ions from the sample under atmospheric or near-atmospheric pressure conditions and transport them to the mass spectrometer inlet. A mass spectrometry detection module is used to detect analyte ions. The mass spectrometry detection module may be at least one of single-stage mass spectrometry, tandem mass spectrometry, or high-resolution mass spectrometry. The data processing and decision-making module is used to perform background reference spectrum acquisition, candidate feature ion set extraction, matching discrimination, exclusion discrimination, screening conclusion and diversion decision output, and can output reports or interface with the quality control system.

[0020] 3. Optional Implementation of Ionization Interface In a preferred embodiment, the ionization module can be implemented using a flow-through reactive soft ionization interface with a radio frequency field and carrier gas flow structure, such as a SICRIT interface, an iSICRIT interface, or an interface with equivalent structure and function; however, the present invention is not limited thereto, and any equivalent technical solution that can achieve sample ionization and introduce it into the mass spectrometer inlet under normal or near-normal pressure conditions falls within the protection scope of the present invention.

[0021] (III) Beneficial Effects Compared with the prior art, the present invention has at least the following beneficial effects: 1) Risk shifting forward: The judgment of "whether there is suspected target residue" is moved forward to the incoming material / on-site decision-making node, and a diversion suggestion for whether to enter the confirmation process is output; 2) Low preparation and high efficiency: Interpretable screening conclusions can be formed without systematic chromatographic separation and complex pretreatment, shortening the time from sample to result; 3) Reduce false positives: The use of peer background reference and the "matching + exclusion" dual discrimination framework reduces false positives / false negatives caused by environmental / system background and spectrum complexity; 4) Industrial compatibility: Compatible with gaseous / liquid / solid samples, covering volatile and transpolar molecular systems, suitable for the engineering deployment of complex systems; 5) Scalable: The reference fingerprint library can be iterated with the target list and formulation baseline, which facilitates the formation of a closed-loop quality control system; 6) Traceability: Sample spectra are paired with background reference spectra, archived, and reported for easy auditing, verification, and cross-batch comparison. Attached Figure Description

[0022] Figure 1 A schematic diagram of the process for rapid screening and triage of target residues in industrial samples.

[0023] Figure 2 This is a block diagram of the overall system structure.

[0024] Figure 3 This is a schematic diagram showing the comparison and difference between the sample spectrum and the background reference spectrum.

[0025] Figure 4 This diagram illustrates the matching discrimination, exclusion discrimination, and three-state output.

[0026] Figure 5 This is a schematic diagram of the sampling / introduction method. Detailed Implementation

[0027] The following embodiments are used to illustrate the present invention, but do not constitute a limitation on the scope of protection of the present invention. Those skilled in the art can make equivalent substitutions without departing from the spirit and essence of the present invention.

[0028] Example 1: Rapid Screening of Industrial Liquid Samples by Dipping (1) Sample: A set of industrial liquid samples, the matrix of which may be polyether, plasticizer or a mixture thereof; the target is low content of target residue or abnormal pollutant.

[0029] (2) Sample introduction: The sample is introduced into the ionization region by dipping or dropping.

[0030] (3) Acquisition: In-situ / environmental ionization and mass spectrometry acquisition are performed to obtain the sample spectrum.

[0031] (4) Background reference: The air background spectrum, system baseline spectrum or blank carrier spectrum are collected within the same or equivalent time window as the background reference spectrum.

[0032] (5) Candidate ion set: Perform difference spectrum / background subtraction on the sample spectrum and the background reference spectrum to extract the candidate feature ion set; and apply at least one of the following rules: the sample / background comparison exceeds the threshold; repeated injections show stable occurrence; isotope / addition / accompanying ion relationship is established; and the mass deviation window is met.

[0033] (6) Discrimination and output: The candidate ion set is matched and discriminated against the reference fingerprint database, and the background and non-target spectrum are excluded and discriminated against. The screening conclusion and diversion suggestions are output.

[0034] (7) Diversion: When the matching judgment indicates a possible hit and the exclusion judgment is valid, it is recommended to enter the confirmation process; otherwise, output "suspected not found" or "re-testing required".

[0035] Example 2: Rapid screening of headspace / deaspiration (1) Sample: The industrial sample is placed in a closed container and equilibrated to form a headspace under normal temperature or controlled temperature conditions; the sample form can be liquid, solid or coating / adhesive, etc.

[0036] (2) Introduction: The headspace gas or gas phase / aerosol generated by desorption is introduced into the ionization region by switching the gas path or valve.

[0037] (3) Background reference: Obtain the blank gas path spectrum by valve switching, or use the blank container headspace spectrum as the background reference spectrum, and compare it with the sample headspace spectrum in the same window or equivalent window.

[0038] (4) Candidate ion set and discrimination: Extract the candidate ion set according to the rules of Example 1 and complete the matching discrimination and exclusion discrimination.

[0039] (5) Output: Output screening conclusions and diversion suggestions for use in time-sensitive scenarios such as incoming material acceptance and odor / emission risk investigation.

[0040] Example 3: Localization of Suspected Positive Cases Based on Fingerprint Consistency (1) Establish reference: Use standard or compliant baseline samples to establish a reference fingerprint set, which includes at least one core ion and its associated ion relationships.

[0041] (2) Sample screening: Rapidly collect and extract candidate ion sets from the sample to be tested.

[0042] (3) Matching discrimination: When the candidate ion set and the reference fingerprint set are consistent within the quality deviation window, and the relevant ions do not constitute the main peak in the background reference spectrum, it is judged as a suspected hit.

[0043] (4) Exclusion criteria: If another spectrum exists but does not satisfy the pairing relationship between the core ion and the accompanying ion, then it is excluded as the main source.

[0044] (5) Triage: Suspected hit samples are given priority to enter the tandem mass spectrometry fragment verification, isotope / addition verification or confirmatory quantification process to shorten the decision-making link.

[0045] Example 4: Repetitive Stability and Three-State Output (1) Perform N repeated introductions (N≥2) on the same sample, and obtain the background reference spectrum synchronously or equivalently in each introduction.

[0046] (2) When the candidate ion set satisfies the preset stability and comparison threshold conditions in at least K repetitions (K≥2), output "Suspected target residue exists".

[0047] (3) If the candidate set is unstable but there is a one-time abnormal peak, output "further verification / retesting is required".

[0048] (4) If the matching judgment is not satisfied and the exclusion judgment prompt is mainly the background or non-target lineage, then output "Suspected non-target residue".

[0049] (5) Three-state output is used to connect with the quality control process: release / retest / send for confirmation.

[0050] Example 5: Optional Implementation of Ionization Interface (1) The ionization module can be implemented using a flow-through reactive soft ionization interface with a radio frequency field and a carrier gas flow structure.

[0051] (2) The interface may be a SICRIT interface, an iSICRIT interface, or an interface with equivalent structure and function.

[0052] (3) Any equivalent technical solution that can achieve sample ionization and introduce it into the mass spectrometer inlet under normal or near-normal pressure conditions falls within the protection scope of this invention. Conclusion

[0053] The above are preferred embodiments of the present invention. Any equivalent substitutions, modifications, or improvements made without departing from the spirit and essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for rapid screening and triage of target residues in situ / ambient ionization mass spectrometry for industrial samples, characterized in that, Includes the following steps: (1) Obtain the industrial sample to be tested, wherein the industrial sample is at least one of gaseous, liquid or solid, covering volatile and transpolar molecular systems, and select at least one sampling or introduction method to introduce the sample into the ionization region; (2) Under normal or near-normal pressure conditions, in-situ / environmental ionization is used to form analytical ions in the sample, and the mass spectrometry detection unit is introduced to collect mass spectrometry data to obtain sample spectrum data; (3) Obtain background reference spectrum data within the same acquisition time window as step (2) or within a window that satisfies the equivalence condition; (4) Based on the sample spectrum and the background reference spectrum, perform background subtraction, difference spectrum calculation or relative intensity adjustment to extract the candidate feature ion set; (5) Match the candidate feature ion set with the reference fingerprint database and exclude environmental background ions or non-target spectrums; (6) Output screening conclusions based on the combined results of matching and exclusion judgments, and output triage decision suggestions to guide whether to proceed to the subsequent confirmation process.

2. The method of claim 1, wherein, The sampling or introduction method includes at least one of the following: direct introduction by dipping or dripping, introduction by carrier, headspace or desorption introduction, and near-field direct introduction of solid or highly viscous samples.

3. The method of claim 1, wherein, The background reference spectrum is obtained by at least one of the following: air background, system baseline, blank carrier, blank container headspace, or blank gas path spectrum obtained by valve switching.

4. The method of claim 1, wherein, The extraction of the candidate feature ion set satisfies at least one of the following rules: a) The intensity of the candidate ion in the sample spectrum is significantly higher than that of the background reference spectrum, exceeding a preset multiple threshold or statistical threshold; b) The candidate ions appear stably during multiple injections or repeated sampling; c) The candidate ions satisfy the preset consistency relationship of isotope peaks, adduct ions or accompanying ions.

5. The method of claim 1, wherein, The matching judgment is based on precise quality matching and setting a preset quality deviation window, or on matching based on a unit resolution quality window, and outputs a consistency score or hit judgment.

6. The method of claim 1, wherein, The exclusion criteria include excluding background ions and / or excluding non-target spectral lines, and the exclusion is based on at least one of the following conditions: background ratio exceeds a threshold, control characteristic ions are missing, or control pairing relationship is not established.

7. The method of claim 1, wherein, The screening results are output in three states: suspected presence of target residue, suspected absence of target residue, and need for further verification or retesting.

8. The method of claim 1, wherein, The subsequent validation process includes at least one of GC-MS, LC-MS / MS, tandem mass spectrometry fragmentation validation, or a quantitative methodology with a standard curve and internal standard strategy.

9. An industrial sample target residue rapid screening and diversion determination system for implementing the method of any one of claims 1-8, characterized in that, include: The sampling / introduction module is used to achieve at least one of the following: dip-type or drop-type introduction, carrier-supported introduction, headspace or desorption introduction, and near-field direct introduction. The ionization module is used to ionize samples in situ / environment under normal or near-normal pressure conditions and form analytical ions. The mass spectrometry detection module is used to detect the analyte ions and output mass spectrometry data; The data processing and decision-making module is used to perform background reference spectrum acquisition, candidate feature ion set extraction, reference fingerprint database matching and discrimination, exclusion discrimination, and output screening conclusions and diversion decision suggestions.

10. The system of claim 9, wherein, The sampling / introduction module includes a heatable desorption unit and / or a gas path valve switching unit to achieve headspace or desorption and acquisition of its blank background reference spectrum.

11. The system according to claim 9, characterized in that, The mass spectrometry detection module is at least one of high-resolution mass spectrometry, tandem mass spectrometry, or single-stage mass spectrometry.

12. The method or system according to any one of claims 1–11, characterized in that, The ionization module is implemented through a flow-through reactive soft ionization interface with a radio frequency field and a carrier gas flow structure. The interface includes a SICRIT interface, an iSICRIT interface, or an in-situ / environmental ionization interface with equivalent structure and function.

13. The method according to claim 1, characterized in that, The data processing and decision-making module associates and stores the sample spectrum with the background reference spectrum in a paired manner, and outputs a report containing the paired spectrum and screening conclusions for quality control archiving or triage decision traceability.

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